Transformation of Follicular Lymphoma to Acute Lymphoblastic Leukemia Xiaoping Sun, MD, PhD; Leo I. Gordon, MD; LoAnn C. Peterson, MD n March 1994, a 56-year-old man underwent lobectomy sies showed a single paratrabecular lymphoid aggregate I of the upper lobe of the right lung and lymph node that suggested involvement by the follicular lymphoma. dissection for poorly differentiated adenocarcinoma. Ma- During the next 6 years, the patient underwent 2 biopsies lignant lymphoma, follicular, small cleaved was identi®ed and 2 ®ne-needle aspiration biopsies of lymph nodes from in multiple paratracheal and hilar lymph nodes. Hema- different sites, and the results of all of these biopsies were toxylin-eosin±stained sections of the lymph nodes showed consistent with the initial diagnosis. Flow cytometric im- a follicular pattern and a predominance of small cleaved munophenotyping was performed on 3 of the lymph node lymphoma cells (Figure, A). Bilateral bone marrow biop- specimens, and all contained CD101 and CD52 clonal B cells (CD191 and CD201) with l surface immunoglobulin light chain restriction. In August of 1999, 5 years after the Accepted for publication March 1, 2002. initial diagnosis, repeated bilateral bone marrow biopsies From the Department of Pathology, Northwestern University Medical School, Chicago, Ill. showed a normocellular bone marrow with 2 nonparatra- Reprints: LoAnn C. Peterson, MD, Department of Pathology, North- becular lymphoid aggregates; these ®ndings were not di- western University Medical School, Feinberg Pavilion, Room 7-344, agnostic for lymphoma. Flow cytometry studies of the 251 East Huron St, Chicago, IL 60611 (e-mail: [email protected]). bone marrow showed no evidence of B-cell clonality. The Arch Pathol Lab MedÐVol 126, August 2002 Transformation of Follicular LymphomaÐSun et al 997 patient's treatment included chlorambucil and radiola- tion to a diffuse large B-cell lymphoma. Transformation beled rituximab. to precursor B-lymphoblastic leukemia/lymphoma is ex- In May 2001, nearly 7 years after the initial diagnosis, tremely rare.1±3 In the current case, the patient had a 7- abnormal blastlike cells were noted in peripheral blood year history of well-established low-grade follicular lym- smears; these cells comprised 8% of white blood cells (Fig- phoma that subsequently progressed to an aggressive ure, B). No peripheral lymphadenopathy was noted. Bone lymphoid neoplasm with extensive involvement of the marrow biopsies showed extensive diffuse in®ltration of blood and bone marrow. This presentation together with bilateral core sections by medium-sized lymphoid cells the blastic appearance of the tumor cells and the ¯ow cy- with immature chromatin and occasional prominent nu- tometric results (terminal deoxynucleotidyl transferase cleoli (Figure, C). Mitotic ®gures were prominent. The as- dim positive and surface immunoglobulin negative) led to pirate smears contained cells with moderately basophilic the diagnosis of lymphoblastic leukemia. The bcl-2±IgH cytoplasm and cytoplasmic vacuoles (Figure, D); these gene rearrangement in the leukemic cells suggests that the cells comprised 40% of nucleated bone marrow cells. Flow lymphoblastic leukemia most likely arose from the low- cytometry studies of the aspirate showed B cells (CD191) grade follicular lymphoma. that were positive for CD10 and dim positive for terminal The mechanism underlying transformation of follicular deoxynucleotidyl transferase but negative for surface or lymphoma is not known, although the transformed lym- cytoplasmic immunoglobulin expression. Polymerase phoma cells may have genetic abnormalities in addition chain reaction of the bone marrow biopsy revealed a bcl- to the t(14;18) translocation. Transformation of follicular 2±IgH gene rearrangement. A diagnosis of precursor B- lymphoma is associated with a poor outcome. The use of lymphoblastic leukemia arising from follicular lymphoma high-dose chemotherapy and autologous stem cell trans- was rendered. The patient was treated with methotrexate plantation in patients with relapsed disease is receiving and leukovorin calcium, and tumor lysis syndrome with increased attention. acute renal failure occurred. The patient's condition sub- References sequently stabilized, and chemotherapy was continued. 1. Gauwerky CE, Hoxie J, Nowell PC, Croce CM. Pre-B-cell leukemia with a Follicular lymphoma usually has an indolent clinical t(8;14) and a t(14;18) translocation is preceded by follicular lymphoma. Onco- gene. 1988;2:431±435. course and may present with waxing and waning enlarge- 2. Fiedler W, Weh HJ, Zeller W, et al. Translocation (14;18) and (8;22) in three ment of the lymph nodes. The natural history of the dis- patients with acute leukemia/lymphoma following centrocytic/centroblastic non- ease is accrual of large cells and transformation to an ag- Hodgkin's lymphoma. Ann Hematol. 1991;63:282±287. 3. Kroft SH, Domiati-Saad R, Finn WG, et al. Precursor B-lymphoblastic trans- gressive lymphoma. Transformation occurs in approxi- formation of grade I follicle center lymphoma. Am J Clin Pathol. 2000;113:411± mately 60% of patients and is almost always transforma- 418. 998 Arch Pathol Lab MedÐVol 126, August 2002 Transformation of Follicular LymphomaÐSun et al.